Many environmental mutagens and carcinogens are known to interact with cellular DNA and RNA in vivo. In these studies synthetic oligo-and polynucleotides will be used as models for nucleic acids to determine the significance of such interactions. This approach uses simple, well- defined systems to yield detailed information on the chemistry of base substitution, and on the accompanying changes in physical properties of the polymers. Biological effects will be assayed in biosynthetic systems which utilize the reacted polynucleotides as templates for replicating and transcribing enzymes. Investigations will proceed along two lines: a) the study of certain known substitutions, e.g. on the O6 position of guanine, which are believed to have special biological significance and b) the development of a screening method for detecting the biological effects of more complicated chemical interactions with suspected carcinogens. Since many carcinogens are known to be metabolically activated, model compounds will be incubated with microsomes in the presence of nucleosides. In this way, reactive species can be detected and elucidated.